The broad objectives of this research are to develop chemical procedures which will aid in the characterization and quantification of those metabolites which are found in uremic patients during hemodialysis, and to learn more about the complex processes which occur in the patient-aritifical kidney system. Utilization of the information gained from this research should facilitate biomedical studies dealing with the interrelative metabolic causes of the uremic syndrome. We have shown that reversed-phase high performance liquid chromatography (HPLC) is an efficient and rapid method for studying metabolic waste compounds in uremic hemodialysate, serum and urine. The method is an order magnitude faster than previousLy used ion-exchange procedures for obtaining total profiles of molecular constituents in physiological fluids. Comparison of uremic serum, hemodialysate, and urine profile has shown that the concentration ratio of dialyzed metabolites is constant for all detected species and that the relative concentration ratios of uremic serum components can be evaluated by analyzing hemodialysate. Clearance levels have been calculated from time-concentration profiles. We have also begun to develop procedures to monitor -NH2 containing species in order to learn more about their physiological role in uremia. Roughly 25 metabolites removed from patients during hemodialysis have thus far been identified. Our efforts will continue along several directions. It is planned to develop procedures to separate, identify and quantify "middle molecular weight" molecules, as well as guanidine derivatives, both of which are suspect as significant uremic toxins. Finally, we hope to optimize the present methods so that they will provide data more rapidly and more efficiently.